Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts
- Université de Toulouse, CNRS, UPS, France
- Université de Toulouse, CNRS, France
Abstract
Osteoclasts are unique in their capacity to degrade bone tissue. To achieve this process, osteoclasts form a specific structure called the sealing zone, which creates a close contact with bone and confines the release of protons and hydrolases for bone degradation. The sealing zone is composed of actin structures called podosomes nested in a dense actin network. The organization of these actin structures inside the sealing zone at the nano scale is still unknown. Here, we combine cutting-edge microscopy methods to reveal the nanoscale architecture and dynamics of the sealing zone formed by human osteoclasts on bone surface. Random illumination microscopy allowed the identification and live imaging of densely packed actin cores within the sealing zone. A cross-correlation analysis of the fluctuations of actin content at these cores indicates that they are locally synchronized. Further examination shows that the sealing zone is composed of groups of synchronized cores linked by a-actinin1 positive filaments, and encircled by adhesion complexes. Thus, we propose that the confinement of bone degradation mediators is achieved through the coordination of islets of actin cores and not by the global coordination of all podosomal subunits forming the sealing zone.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figures 1, 2, 3, 4 and 5.
Article and author information
Author details
Brigitte Raynaud-Messina
Funding
Agence Nationale de la Recherche (ANR16-CE13)
- Christel Vérollet
Fondation pour la Recherche Médicale (FRM DEQ2016 0334894)
- Isabelle Maridonneau-Parini
Human Frontier Science Program (RGP0035/2016)
- Isabelle Maridonneau-Parini
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Monocytes from healthy subjects were provided by Etablissement Français du Sang (EFS), Toulouse, France, under contract 21/PLER/TOU/IPBS01/20130042. According to articles L12434 and R124361 of the French Public Health Code, the contract was approved by the French Ministry of Science and Technology (agreement number AC 2009921). Written informed consents were obtained from the donors before sample collection.
Reviewing Editor
- Maria Grano, University of Bari, Italy
Publication history
- Received: November 16, 2021
- Accepted: June 20, 2022
- Accepted Manuscript published: June 21, 2022 (version 1)
- Accepted Manuscript updated: June 23, 2022 (version 2)
Copyright
© 2022, Portes et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts
eLife 11:e75610.
https://doi.org/10.7554/eLife.75610
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